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Edin Zukić

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Growing body of evidence suggests that molecular markers are an important prognostic marker for non-small lung cancer (NSCLC). Using targeted therapy based on these markers leads to improved outcomes in lung adenocarcinoma. However, progress of targeted therapy in squamous lung cancer is still modest. p16(ink) protein acts as tumor suppressor and vascular endothelial growth factor (VEGF) promotes tumor angiogenesis. Purpose of this study was to evaluate the difference in p16(ink4) and VEGF expression between squamous and adenocarcinoma of the lung; to evaluate the relationship of p16(ink4) and VEGF expression to survival outcomes in NSCLC patients, and the difference of their prognostic values between squamous and adenocarcinoma subtypes. 100 NSCLC patients (50 squamous and 50 adenocarcinoma) and 80 healthy individuals were included. p16(ink4) and VEGF proteins were immunohistochemicaly detected on formalin-fixed tissues. One- and 2-year progression-free survival (PFS) and overall survival (OS) were observed. p16(ink4) expression was significantly lower in squamous type compared to adenocarcinoma. In both squamous and adenocarcinoma, high VEGF expression correlated with worse 1-year PFS and OS, but only with worse 2-year PFS. Low p16(ink4) expression correlated with worse 1- and 2-year PFS, as well as OS, in both NSCLC subtypes. In squamous lung cancer p16(ink4) expression was an independent negative prognostic marker. Our study confirms the difference of p16(ink4) protein expression in squamous and adenocarcinoma of the lung. Besides anti-VEGF therapy, the regulation of p16(ink4) expression could have a therapeutic potential in NSCLC, especially in squamous lung cancer.

Molecular regulatory mechanisms of lung cancer initiation and progression are poorly understood. Role of micro RNA (miRNA) 19a in lung cancer is still controversial, as well. Treatments of non-small-cell lung cancer (NSCLC), particularly of the squamous subtype are limited. However increasing evidence point many molecular markers as potential prognostic and therapeutic tools. Purpose of this study was to evaluate differences in miR-19a, as well as miR-126 and let-7b expression profiles between NSCLC tumor tissue and healthy lung tissue. Also, the purpose was to evaluate the relationship of miR-19a, miR-126 and let-7b expression to survival outcomes in NSCLC patients but to evaluate the differences of their prognostic values between squamous and adenocarcinoma subtypes. 50 non-small lung cancer patients (32 squamous and 18 adenocarcinoma) and 45 healthy individuals were included. miRNA expression was detected by quantitative real-time polymerase chain reaction. Microvascular density was immunohistochemicaly quantified by factor VIII-related antigen. One- and two-years survival outcomes were observed. Expression of anti-angiogenic miR-19a, miR-126 and let-7b were significantly lower in tumour tissue compared to control lung tissue. Low miRNAs expression correlated with worse progression-free survival in both squamous and adenocarcinoma of the lung. Poor overall survivals were associated with low miRNAs expression only in the squamous lung cancer. Besides miR-126 and let-7b, our observations confirm also anti-angiogenic role of miR-19a in NSCLC patients and suggest the potential new target therapy in squamous lung cancer.

Objective: The primary goal of this study was to determine the difference of abundance of CD4+, CD8+ and CD56+ bronchoalveolar fluid’s lymphocytes and their subpopulations between cancerous lung and healthy lung from the same patient. Methods: Mini-bronchoalveolar lavage was taken from 55 patients from lung with cancer and healthy lung. After laboratory processing and addition of CD4, CD8, CD27, CD28 and CD56 antibody, the material was analyzed by flow cytometer. Results from lung with cancer were compared to the ones from the healthy lung. The examined patients were the test and the control group at the same time. Results: CD27+28+ forms of CD4+ and CD8+ lymphocytes are more activated in the cancerous lung compared to healthy lung, while the CD27-28- forms are less activated in diseased lung. CD4+ forms of CD56+ lymphocytes are more activated in cancerous lung compared to the health lung, while the CD8+ forms are less activated in diseased lung. Conclusion: Immature helper and cytotoxic T lymphocyte response, as well as regulatory NK and NKT cell response are more activated in cancerous lung compared to the health lung of the same patient.

Lymphangioma is a malformation composed of a mass of dilated lymph vessels typically found in the cervical region in children. Mediastinal lymphangioma is a rare condition and accounts for 0.01% to 4.5% of all mediastinal tumors. Only 4 cases of mediastinal lymphangioma involving the heart and great vessels in adults have been described in the available literature. Extremely rarely, lymphangiomas occur as a generalized lymphangiomatosis. We present a case of a woman who coughed up small amounts of fresh blood during 6 months and showed signs of cardiac failure. Several years previously, the patient underwent surgical removal of cystic lymphangiomas from the left ovary, both fallopian tubes and small intestine. A chest radiograph showed an 8-cm round shadow located in the middle lobe. A computerized tomography (CT) scan of the chest with contrast verified the existence of a cyst in the anterior mediastinum. The radiologist suggested that the cyst could have originated in the pericardium. One small cyst also appeared in the projection of the left cardiophrenic sinus. A CT scan with contrast of the patient’s abdomen showed multiple cystic formations in the liver, spleen, kidneys, and left parapelvic region. A fine-needle biopsy of the mediastinal tumor verified the cystic lymphangioma, which was then completely removed surgically. A pathohistological examination confirmed the existence of cystic lymphangioma. The patient was discharged after a period of recovery.

AIM To determinate the difference of abundance of CD4+, CD8+ and CD56+ bronchoalveolar fluid's lymphocytes and their subpopulations between non- and small cell lung cancer. Also, the differences of abundance of examined lymphocytes were compared between main clinical stages of lung cancer. METHODS Mini-bronchoalveolar lavate was taken from lungs of 55 patients with cancer. After laboratory processing and adding CD3, CD4, CD8, CD27, CD28 and CD56 antibody, the material was analysed by flow cytometer. Results of Mini-BAL for non- and small cell lung cancer were compared, as well as the different clinical stages of the disease. RESULTS Immature and regulatory forms of lymphocytes are more activated, while mature and activated forms are less activated in small cell lung cancer compared to non small type. With an increase of the clinical stage of disease, immunological reaction of T lymphocytes is better expressed because of increasing of abundance of immature and regulatory forms of different subpopulations of lymphocytes. CONCLUSION All components of local CD4+ and CD8+ T lymphocyte, as well as NK and NKT cells response were more activated in lungs with small cell lung cancer, and these reactions were more expressed with an increase in the clinical stage.

Early detection and treatment of preneoplastic lesions represents an obvious option to reduce morbidity and mortality from lung malignancies. Until now, radiological detection, sputum cytology, and autofluorescence have shown limited effectiveness as screening methods. Novel technologies such as Narrow Band Imaging (NBI) are showing promising results, but new studies are still needed to evaluate their use as screening methods. Together with early detection, adequate methods of lesion treatment, such as argon plasma coagulation, are needed. This case report concerns a 45-year-old man who was referred for bronchoscopy after his annual checkup. Using NBI technology, a preneoplastic lesion was identified, and treated using argon plasma coagulation. Our experience has shown us that both NBI screening and argon plasma coagulation are very promising, easily implemented, methods.

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